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Natural Products and related Redox

Catalysts: Basic Research and Applications

in Medicine and Agriculture

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Protein-ligand docking study: diterpenes from Juniperus brevifolia as

anticancer and antimicrobial agents

Inês J. Sousa,a Miguel X. Fernandes,

a Ana M. L. Seca

b

aCentro de Química da Madeira, Campus da Penteada, University of Madeira, 9000-390 Funchal, Portugal; bDCTD, University of Azores, 9501-801 Ponta Delgada,Portugal.

From leaves of Juniperus brevifolia, an endemic conifer from Azores, were isolated

and structurally characterized, several dehydroabietane and sandaracopimarane

derivatives.[1]

Some of them (1-4), displayed antiproliferative activity against cancer cell

lines (HeLa, A-549 and MCF-7) and bactericidal effect against Bacillus cereus at different

concentrations tested.[2]

However, it is not known how these compounds interact with most

often proteins involved in the antimicrobial and cytotoxic mechanisms. Protein-ligand

docking is mainly used to predict (energy and conformation wise) how small molecules

bind to a protein of known 3D structure and to predict possible molecular targets for a set

of compounds. In this work, the docking studies were performed, using the FlexScreen

program, in order to pick molecular targets from a large set of common anticancer (63) and

antimicrobial (39) targets to the selected compounds 1-4. The predicted interactions

established between the compounds under study and the anticancer targets revealed that the

compounds 1 and 3 interact preferentially with phosphatidylinositol-3,4,5-trisphosphate 5-

phosphatase 2, whereas compounds 2 and 4 interact preferentially with human

mitochondrial peptide deformylase and α-tubulin, respectively. Studying the interactions

between the compounds 1 and 3 and the antimicrobial targets we predict that these

compounds interact preferentially with RNA polymerase and peptide deformylase. These

results provide additional understanding of the cytotoxic and antimicrobial effects of

diterpenes studied. These preliminary computational docking predictions of therapeutic

targets were established working with just 4 compounds, and to obtain more reliable

predictions the number of compounds needs to be increased.

Acknowledgments: Thanks are due to the University of Azores, FCT, FEDER, BIOPHARMAC - MAC/1/C104 and Project PEst-OE/QUI/UI0674/2011.

References

[1] Seca, A. M. L.; Silva, A. M. S.; Bazzocchi, I. L.; Jimenez, I. A. Phytochemistry 2008, 69, 498.

[2] Moujir, L. M.; Seca, A. M.L.; Araújo, L.; Silva, A. M.S.; Barreto, M. C. Fitoterapia 2011, 82, 225.